Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Doctor of Philosophy

Program

Medical Biophysics

Supervisor

Ellis, Christopher G

2nd Supervisor

Guo, Linrui R

Co-Supervisor

Abstract

Cardiopulmonary bypass can result in multiple organ failure due to mechanisms of ischemia reperfusion injury and the systemic inflammatory response syndrome. The primary objective of this thesis was to investigate and monitor the microvasculature in cardiac surgery patients using multiple methodologies and real-time monitoring techniques. The purpose of our first study was to determine whether pulsatile blood flow during bypass improves microvascular perfusion compared to non-pulsatile flow. We found that changes in sublingual mucosal microcirculation using orthogonal polarization spectral imaging correlate with indices of thenar muscle tissue oxygen saturation and its recovery during a vascular occlusion test using near-infrared spectroscopy in both groups. There were significantly fewer normally perfused vessels, along with impaired microvascular responsiveness and elevated levels of lactate in the non-pulsatile group. Although these technologies help to better understand the pathophysiology of acute circulatory failure, a need exists for improved monitors that can continuously track real-time changes in the microcirculation. Our subsequent studies involved the application of a custom broadband continuous wave near-infrared monitor to determine the feasibility of tracking microvascular hemoglobin content as a surrogate for red blood cell (RBC) flow in skeletal muscle during non-pulsatile bypass. We measure changes in optical density at the isosbestic wavelength as an index of change in hemoglobin over time. The changes in optical density relative to baseline values were continuously monitored throughout the procedure, and showed a positive correlation with various interventions during bypass and with potentially negative outcomes. In our third study we applied continuous wavelet transform analysis to the near-infrared data to reflect the dynamic variability in RBC distribution within the microvasculature as an indicator of autoregulation. We showed signal power composition varied within and between patients at all time points, and shifting of power distribution from high to low frequency ranges, and vice versa, in relation to specific events during the procedure. These studies support the potential for clinical devices that can be easily interpreted by a clinician in real-time to guide therapeutic targets and improve clinical outcomes. Our current research and related future work is an important first step and compelling pre-requisite for such a monitor.

Summary for Lay Audience

To repair the heart during surgery, the pumping of the heart must be stopped. To keep the patient alive they are connected to a machine that oxygenates the blood and pumps it throughout the body. However cardiopulmonary bypass can cause inflammation affecting the smallest blood vessels of the body called the microcirculation. My objective was to investigate the effects of bypass on these small vessels using different types of imaging devices. During bypass blood can be pumped continuously without a pulse or with an artificial pulse added. In our first study we investigated whether blood flow to the microcirculation changes when comparing flow modes. We found that pulsatile flow improved blood flow through the microcirculation under the tongue compared to non-pulsatile, and pulsatility also improved how quickly blood flow was restored to a muscle at the base of the thumb following a brief period of occlusion by a blood pressure cuff. As these technologies require the intervention of a health care provider and provide only a snapshot of the patient’s condition, our second study investigated new technology that would continuously collect information. This device was placed on the thigh muscle and monitored red blood cell hemoglobin levels as blood flowed through the microcirculation under non-pulsatile flow conditions. We successfully tracked changes in hemoglobin levels in relation to key events occurring during bypass. Since hemoglobin carries oxygen, our third study investigated if the microcirculation changes its pattern of delivery during the course of surgery. As the microcirculation regulates the delivery of blood and oxygen to the tissue it causes small oscillations in hemoglobin levels over a range of frequencies. Our analysis measured the strength of different frequency ranges generated by the microcirculation. We showed that power versus frequency varied within each patient at various time points, and that differences also existed between patients. We noticed power shifting from one frequency to another during particular interventions which correlated with patient outcomes. In summary, we successfully monitored the microcirculation during bypass. These studies demonstrate the potential for new microvascular monitoring, and are an important first step in development of such a monitor.

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